Understanding Viral Evolution and Pathogenesis using Genomics, Functional Assays, and Structural Biology Techniques

Karla Strucker (J. Craig Venter Institute)

High-throughput, whole-genome, next-generation sequencing (NGS) of viruses has greatly expanded the availability of genomic sequence data and the scope of analyses that can be conducted to better understand viral evolution, emergence, and pathogenesis. For example, the J. Craig Venter Institute (JCVI) has sequenced over 15,000 coding-complete influenza virus genomes since 2005, with over half of those being completed in the past 3 years. We use the viral genomic data, along with available clinical data, to perform phylogenetic analyses of viral evolution over time and to identify genetic variants that may be causing unique phenotypes of interest, such as immune escape or increased pathogenesis. We couple synthetic genomics with viral reverse genetics systems to rescue viruses of interest and/or express mutated viral proteins for testing in functional assays, and we hope to expand these studies using structural data from X-ray crystallographic, cryo-EM, and SANS experiments. Influenza virus, filovirus, and rotavirus examples will be presented.

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